Atrial fibrillation is the most common cardiac arrhythmia and is associated with substantial morbidity and mortality. Its incidence and prevalence are increasing and it represents a growing clinical and economic burden (current prevalence is of 2% in the general population). In addition to severe clinical symptoms like palpitations, dizziness, dyspnea and others, atrial fibrillation is the single most important factor for ischemic stroke in the population over 75 years of age. Overall, atrial fibrillation accounts for over 5% of hospital admissions for cardiovascular diseases. In about 90% of cases atrial fibrillation occurs in the presence of other cardiac diseases, like hypertensive heart disease, congestive heart failure or cardiac valve diseases. In only 10% of cases does atrial fibrillation develop in the absence of cardiac abnormalities (“lone” atrial fibrillation). Three forms of atrial fibrillation can be differentiated: (1) paroxysmal atrial fibrillation characterized by self-terminating atrial fibrillation episodes with durations that vary from seconds to days; (2) persistent atrial fibrillation that lasts indefinitely until terminated by medical interventions; (3) permanent atrial fibrillation that cannot be terminated by pharmacological or electrical cardioversion.
Studies have shown that atrial fibrillation results from multiple re-entrant electrical wavelets that move randomly around the atria. These wavelets are initiated by electrical triggers, commonly located in the myocardial sleeves extending from the left atrium to the proximal 5-6 cm portions of the pulmonary veins. Once atrial fibrillation is triggered, changes in the atria are produced (atria remodelling) which affect to its electrical, mechanical and metabolic properties, responsible of arrhythmia persistence. Ventricular rate control in presence of atrial fibrillation is elevated and if rate control can not be reduced with medical treatment, leads to ventricular dilatation and impairment of systolic function, commonly referred to as tachycardiomyopathy. Stroke and thromboembolism are a major cause of mortality and morbidity associated with atrial fibrillation, and the underlying pathophysiological basis of this is a prothrombotic or hypercoagulable state in association with abnormalities of blood flow (atrial stasis, for example) and endothelial or endocardial damage.
As in other subspecialties in cardiology, important progress has been made in the diagnosis and treatment of cardiac arrhythmias during the last four decades. In spite of many advances, a really cure of cardiac arrhythmias and the prevention of sudden arrhythmic death is in a minority of the patients. Nowadays atrial fibrillation therapy encompasses the reduction of atrial fibrillation-related symptoms, prevention of thromboembolic complications, and termination of the arrhythmia when appropriate.
In general there are two approaches in the management of atrial fibrillation: a) management of the arrhythmia itself and b) reduction of the thromboembolic risk (cf. M. B. Iqbal et al., “Recent developments in atrial fibrillation”, British Medical Journal 2005, vol. 330, pp. 238-43). Management of the arrhythmia encompasses rhythm control (restoration and maintenance of sinus rhythm) and rate control. Pharmacologically, rhythm and rate control are managed with antiarrhythmic drugs (class I and class III antiarrhythmic agents). Examples of them which are used nowadays are flecainide, propafenone, amiodarone, dofetilide, ibutilide and sotalol. Non-pharmacologically, rhythm and rate control are managed with electrical cardioversion, atrial based pacing, implantable atrial defibrillator, radiofrequency catheter ablation and surgical maze procedure.
Reduction of the thromboembolic risk and thus, stroke prevention are of major importance in treatment strategy. Pharmacologically, aspirin and warfarin are recommended in the majority of patients to prevent atrial thrombus formation and thromboembolic events. Pooled data from trials with high risk patients show that warfarin is better than aspirin in preventing strokes, but the risk of major haemorrhage with warfarin is twice that with aspirin. Anyway, anticoagulation treatment needs to be tailored individually on the basis of age, comorbidities and contraindications. Non-pharmacologically, reduction of the thromboembolic risk is currently managed with obliteration of left atrial appendage or with catheter (procedure under research).
Recent research has highlighted new approaches to both pharmacological and non-pharmacological management strategies. The most promising agents are angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blocking drugs. Protease inhibitors, phosphatases of sufficient selectivity and specificity or antioxidants may also offer novel therapeutic strategies to reduce or reverse structural changes, atrial dilation, and contractile dysfunction. However, the problem of treatment of atrial fibrillation is still far from being solved satisfactorily.